ACTS_HUMAN
ID ACTS_HUMAN Reviewed; 377 AA.
AC P68133; P02568; P99020; Q5T8M9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Actin, alpha skeletal muscle;
DE AltName: Full=Alpha-actin-1;
DE Contains:
DE RecName: Full=Actin, alpha skeletal muscle, intermediate form;
DE Flags: Precursor;
GN Name=ACTA1; Synonyms=ACTA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=6190133; DOI=10.1093/nar/11.11.3503;
RA Hanauer A., Levin M., Heilig R., Daegelen D., Kahn A., Mandel J.-L.;
RT "Isolation and characterization of cDNA clones for human skeletal muscle
RT alpha actin.";
RL Nucleic Acids Res. 11:3503-3516(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2907503; DOI=10.1016/0888-7543(88)90123-1;
RA Taylor A., Erba H.P., Muscat G.E.O., Kedes L.;
RT "Nucleotide sequence and expression of the human skeletal alpha-actin gene:
RT evolution of functional regulatory domains.";
RL Genomics 3:323-336(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NEM3 TYR-42; PRO-96; SER-117;
RP VAL-134; ASP-184; CYS-185; HIS-258; VAL-261; LEU-265; LYS-282; GLY-288 AND
RP PHE-372, AND VARIANTS MPCETM ARG-17 AND LEU-165.
RX PubMed=10508519; DOI=10.1038/13837;
RA Nowak K.J., Wattanasirichaigoon D., Goebel H.H., Wilce M., Pelin K.,
RA Donner K., Jacob R.L., Hubner C., Oexle K., Anderson J.R., Verity C.M.,
RA North K.N.;
RT "Mutations in the skeletal muscle alpha-actin gene in patients with actin
RT myopathy and nemaline myopathy.";
RL Nat. Genet. 23:208-212(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH TTID.
RX PubMed=10958653; DOI=10.1093/hmg/9.14.2141;
RA Hauser M.A., Horrigan S.K., Salmikangas P., Torian U.M., Viles K.D.,
RA Dancel R., Tim R.W., Taivainen A., Bartoloni L., Gilchrist J.M.,
RA Stajich J.M., Gaskell P.C., Gilbert J.R., Vance J.M., Pericak-Vance M.A.,
RA Carpen O., Westbrook C.A., Speer M.C.;
RT "Myotilin is mutated in limb girdle muscular dystrophy 1A.";
RL Hum. Mol. Genet. 9:2141-2147(2000).
RN [9]
RP INTERACTION WITH USP25.
RX PubMed=16501887; DOI=10.1007/s00018-005-5533-1;
RA Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.;
RT "The ubiquitin-specific protease USP25 interacts with three sarcomeric
RT proteins.";
RL Cell. Mol. Life Sci. 63:723-734(2006).
RN [10]
RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION).
RX PubMed=19015515; DOI=10.1073/pnas.0808082105;
RA Kudryashov D.S., Durer Z.A., Ytterberg A.J., Sawaya M.R., Pashkov I.,
RA Prochazkova K., Yeates T.O., Loo R.R., Loo J.A., Satchell K.J., Reisler E.;
RT "Connecting actin monomers by iso-peptide bond is a toxicity mechanism of
RT the Vibrio cholerae MARTX toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:18537-18542(2008).
RN [11]
RP MALONYLATION AT LYS-63.
RX PubMed=21908771; DOI=10.1074/mcp.m111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W.,
RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J.,
RA Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [12]
RP METHYLATION AT LYS-86, AND DEMETHYLATION BY ALKBH4.
RX PubMed=23673617; DOI=10.1038/ncomms2863;
RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., Niu Y.,
RA Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., He C.,
RA Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.;
RT "ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.";
RL Nat. Commun. 4:1832-1832(2013).
RN [13]
RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION).
RX PubMed=26228148; DOI=10.1126/science.aab4090;
RA Heisler D.B., Kudryashova E., Grinevich D.O., Suarez C., Winkelman J.D.,
RA Birukov K.G., Kotha S.R., Parinandi N.L., Vavylonis D., Kovar D.R.,
RA Kudryashov D.S.;
RT "ACD toxin-produced actin oligomers poison formin-controlled actin
RT polymerization.";
RL Science 349:535-539(2015).
RN [14]
RP METHYLATION AT HIS-75.
RX PubMed=30626964; DOI=10.1038/s41586-018-0821-8;
RA Wilkinson A.W., Diep J., Dai S., Liu S., Ooi Y.S., Song D., Li T.M.,
RA Horton J.R., Zhang X., Liu C., Trivedi D.V., Ruppel K.M.,
RA Vilches-Moure J.G., Casey K.M., Mak J., Cowan T., Elias J.E.,
RA Nagamine C.M., Spudich J.A., Cheng X., Carette J.E., Gozani O.;
RT "SETD3 is an actin histidine methyltransferase that prevents primary
RT dystocia.";
RL Nature 565:372-376(2019).
RN [15]
RP VARIANTS NEM3 SER-117; MET-138; GLY-185; CYS-270 AND LEU-359.
RX PubMed=11333380; DOI=10.1086/320605;
RA Ilkovski B., Cooper S.T., Nowak K., Ryan M.M., Yang N., Schnell C.,
RA Durling H.J., Roddick L.G., Wilkinson I., Kornberg A.J., Collins K.J.,
RA Wallace G., Gunning P., Hardeman E.C., Laing N.G., North K.N.;
RT "Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin
RT gene.";
RL Am. J. Hum. Genet. 68:1333-1343(2001).
RN [16]
RP REVIEW ON VARIANTS.
RX PubMed=12921789; DOI=10.1016/s0960-8966(03)00101-9;
RA Sparrow J.C., Nowak K.J., Durling H.J., Beggs A.H., Wallgren-Pettersson C.,
RA Romero N., Nonaka I., Laing N.G.;
RT "Muscle disease caused by mutations in the skeletal muscle alpha-actin gene
RT (ACTA1).";
RL Neuromuscul. Disord. 13:519-531(2003).
RN [17]
RP VARIANTS NEM3 VAL-134 AND ARG-271.
RX PubMed=11166164; DOI=10.1016/s0960-8966(00)00167-x;
RA Jungbluth H., Sewry C.A., Brown S.C., Nowak K.J., Laing N.G.,
RA Wallgren-Pettersson C., Pelin K., Manzur A.Y., Mercuri E., Dubowitz V.,
RA Muntoni F.;
RT "Mild phenotype of nemaline myopathy with sleep hypoventilation due to a
RT mutation in the skeletal muscle alpha-actin (ACTA1) gene.";
RL Neuromuscul. Disord. 11:35-40(2001).
RN [18]
RP VARIANTS NEM3 LEU-37; LEU-40; TYR-42; ARG-43; ASN-66; LEU-75; ARG-75;
RP LEU-77; ALA-79; LYS-85; ALA-136; ASP-148; GLY-181; ASP-184; GLY-185;
RP SER-199; GLY-226; VAL-229; ILE-229; ARG-248; ASP-253; CYS-270; HIS-281;
RP LYS-282; GLY-288 AND GLN-375.
RX PubMed=15236405; DOI=10.1002/ana.20157;
RA Agrawal P.B., Strickland C.D., Midgett C., Morales A., Newburger D.E.,
RA Poulos M.A., Tomczak K.K., Ryan M.M., Iannaccone S.T., Crawford T.O.,
RA Laing N.G., Beggs A.H.;
RT "Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin
RT gene mutations.";
RL Ann. Neurol. 56:86-96(2004).
RN [19]
RP VARIANTS CFTD PRO-223; VAL-294 AND SER-334.
RX PubMed=15468086; DOI=10.1002/ana.20260;
RA Laing N.G., Clarke N.F., Dye D.E., Liyanage K., Walker K.R., Kobayashi Y.,
RA Shimakawa S., Hagiwara T., Ouvrier R., Sparrow J.C., Nishino I.,
RA North K.N., Nonaka I.;
RT "Actin mutations are one cause of congenital fibre type disproportion.";
RL Ann. Neurol. 56:689-694(2004).
RN [20]
RP VARIANTS NEM3 ILE-68; LYS-74; SER-117; MET-138; LEU-165; MET-165; GLY-185;
RP CYS-270 AND LEU-359.
RX PubMed=15198992; DOI=10.1093/hmg/ddh185;
RA Ilkovski B., Nowak K.J., Domazetovska A., Maxwell A.L., Clement S.,
RA Davies K.E., Laing N.G., North K.N., Cooper S.T.;
RT "Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused
RT by abnormal folding, aggregation and altered polymerization of mutant actin
RT isoforms.";
RL Hum. Mol. Genet. 13:1727-1743(2004).
RN [21]
RP VARIANTS NEM3 TYR-3 AND ALA-336.
RX PubMed=15520409; DOI=10.1136/jmg.2004.020271;
RA Kaindl A.M., Rueschendorf F., Krause S., Goebel H.-H., Koehler K.,
RA Becker C., Pongratz D., Mueller-Hoecker J., Nuernberg P.,
RA Stoltenburg-Didinger G., Lochmueller H., Huebner A.;
RT "Missense mutations of ACTA1 cause dominant congenital myopathy with
RT cores.";
RL J. Med. Genet. 41:842-848(2004).
RN [22]
RP VARIANTS NEM3 ASP-270 AND GLU-375.
RX PubMed=15336687; DOI=10.1016/j.nmd.2004.05.016;
RA Ohlsson M., Tajsharghi H., Darin N., Kyllerman M., Oldfors A.;
RT "Follow-up of nemaline myopathy in two patients with novel mutations in the
RT skeletal muscle alpha-actin gene (ACTA1).";
RL Neuromuscul. Disord. 14:471-475(2004).
RN [23]
RP VARIANT NEM3 MET-165.
RX PubMed=16427282; DOI=10.1016/j.nmd.2005.11.004;
RA Hutchinson D.O., Charlton A., Laing N.G., Ilkovski B., North K.N.;
RT "Autosomal dominant nemaline myopathy with intranuclear rods due to
RT mutation of the skeletal muscle ACTA1 gene: clinical and pathological
RT variability within a kindred.";
RL Neuromuscul. Disord. 16:113-121(2006).
RN [24]
RP VARIANT NEM3 GLU-338.
RX PubMed=16945537; DOI=10.1016/j.nmd.2006.07.005;
RA D'Amico A., Graziano C., Pacileo G., Petrini S., Nowak K.J., Boldrini R.,
RA Jacques A., Feng J.-J., Porfirio B., Sewry C.A., Santorelli F.M.,
RA Limongelli G., Bertini E., Laing N., Marston S.B.;
RT "Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with
RT ACTA1 K336E mutation.";
RL Neuromuscul. Disord. 16:548-552(2006).
RN [25]
RP CHARACTERIZATION OF VARIANT CFTD VAL-294.
RX PubMed=17387733; DOI=10.1002/ana.21112;
RA Clarke N.F., Ilkovski B., Cooper S., Valova V.A., Robinson P.J., Nonaka I.,
RA Feng J.-J., Marston S., North K.;
RT "The pathogenesis of ACTA1-related congenital fiber type disproportion.";
RL Ann. Neurol. 61:552-561(2007).
RN [26]
RP CHARACTERIZATION OF VARIANT NEM3 MET-165.
RX PubMed=17705262; DOI=10.1002/ana.21200;
RA Domazetovska A., Ilkovski B., Kumar V., Valova V.A., Vandebrouck A.,
RA Hutchinson D.O., Robinson P.J., Cooper S.T., Sparrow J.C., Peckham M.,
RA North K.N.;
RT "Intranuclear rod myopathy: molecular pathogenesis and mechanisms of
RT weakness.";
RL Ann. Neurol. 62:597-608(2007).
RN [27]
RP VARIANT NEM3 ASN-328, AND CHARACTERIZATION OF VARIANT NEM3 ASN-328.
RX PubMed=22442437; DOI=10.1212/wnl.0b013e31824e8ebe;
RA Jain R.K., Jayawant S., Squier W., Muntoni F., Sewry C.A., Manzur A.,
RA Quinlivan R., Lillis S., Jungbluth H., Sparrow J.C., Ravenscroft G.,
RA Nowak K.J., Memo M., Marston S.B., Laing N.G.;
RT "Nemaline myopathy with stiffness and hypertonia associated with an ACTA1
RT mutation.";
RL Neurology 78:1100-1103(2012).
RN [28]
RP VARIANT NEM3 CYS-358.
RX PubMed=23650303; DOI=10.1542/peds.2012-1139;
RA Gatayama R., Ueno K., Nakamura H., Yanagi S., Ueda H., Yamagishi H.,
RA Yasui S.;
RT "Nemaline myopathy with dilated cardiomyopathy in childhood.";
RL Pediatrics 131:E1986-E1990(2013).
RN [29]
RP INVOLVEMENT IN SHPM, VARIANT SHPM ASP-197, CHARACTERIZATION OF VARIANT SHPM
RP ASP-197, AND CHARACTERIZATION OF VARIANT NEM3 GLY-288.
RX PubMed=25938801; DOI=10.1001/jamaneurol.2015.37;
RA Zukosky K., Meilleur K., Traynor B.J., Dastgir J., Medne L., Devoto M.,
RA Collins J., Rooney J., Zou Y., Yang M.L., Gibbs J.R., Meier M.,
RA Stetefeld J., Finkel R.S., Schessl J., Elman L., Felice K., Ferguson T.A.,
RA Ceyhan-Birsoy O., Beggs A.H., Tennekoon G., Johnson J.O., Boennemann C.G.;
RT "Association of a Novel ACTA1 Mutation With a Dominant Progressive
RT Scapuloperoneal Myopathy in an Extended Family.";
RL JAMA Neurol. 72:689-698(2015).
RN [30]
RP VARIANTS NEM3 ARG-72 AND VAL-116.
RX PubMed=25635128; DOI=10.1136/jmedgenet-2014-102819;
RA Chae J.H., Vasta V., Cho A., Lim B.C., Zhang Q., Eun S.H., Hahn S.H.;
RT "Utility of next generation sequencing in genetic diagnosis of early onset
RT neuromuscular disorders.";
RL J. Med. Genet. 52:208-216(2015).
RN [31]
RP VARIANT NEM3 SER-17.
RX PubMed=29274205; DOI=10.1002/ajmg.a.38577;
RA Ahmed A.A., Skaria P., Safina N.P., Thiffault I., Kats A., Taboada E.,
RA Habeebu S., Saunders C.;
RT "Arthrogryposis and pterygia as lethal end manifestations of genetically
RT defined congenital myopathies.";
RL Am. J. Med. Genet. A 176:359-367(2018).
CC -!- FUNCTION: Actins are highly conserved proteins that are involved in
CC various types of cell motility and are ubiquitously expressed in all
CC eukaryotic cells.
CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a
CC structural filament (F-actin) in the form of a two-stranded helix. Each
CC actin can bind to 4 others. Interacts with alpha-actinin (By
CC similarity). Identified in a complex composed of ACTA1, COBL, GSN AND
CC TMSB4X (By similarity). Interacts with TTID (PubMed:10958653).
CC Interacts (via its C-terminus) with USP25; the interaction occurs for
CC all USP25 isoforms but is strongest for isoform USP25m in muscle
CC differentiating cells (PubMed:16501887). {ECO:0000250|UniProtKB:P68135,
CC ECO:0000269|PubMed:10958653, ECO:0000269|PubMed:16501887}.
CC -!- INTERACTION:
CC P68133; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-367510, EBI-10254793;
CC P68133; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-367510, EBI-1383687;
CC P68133; Q0VD86: INCA1; NbExp=3; IntAct=EBI-367510, EBI-6509505;
CC P68133; Q6ZQX7-4: LIAT1; NbExp=3; IntAct=EBI-367510, EBI-25830459;
CC P68133; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-367510, EBI-10171633;
CC P68133; Q9H7C4: SYNC; NbExp=3; IntAct=EBI-367510, EBI-11285923;
CC P68133; P17024: ZNF20; NbExp=3; IntAct=EBI-367510, EBI-717634;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- PTM: Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or
CC MICAL3) to form methionine sulfoxide promotes actin filament
CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The
CC (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin
CC repolymerization. {ECO:0000250|UniProtKB:P68134}.
CC -!- PTM: Monomethylation at Lys-86 (K84me1) regulates actin-myosin
CC interaction and actomyosin-dependent processes. Demethylation by ALKBH4
CC is required for maintaining actomyosin dynamics supporting normal
CC cleavage furrow ingression during cytokinesis and cell migration.
CC {ECO:0000269|PubMed:23673617}.
CC -!- PTM: Methylated at His-75 by SETD3. {ECO:0000269|PubMed:30626964}.
CC -!- PTM: (Microbial infection) Monomeric actin is cross-linked by
CC V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins
CC mediate the cross-link between Lys-52 of one monomer and Glu-272 of
CC another actin monomer, resulting in formation of highly toxic actin
CC oligomers that cause cell rounding (PubMed:19015515). The toxin can be
CC highly efficient at very low concentrations by acting on formin
CC homology family proteins: toxic actin oligomers bind with high affinity
CC to formins and adversely affect both nucleation and elongation
CC abilities of formins, causing their potent inhibition in both profilin-
CC dependent and independent manners (PubMed:26228148).
CC {ECO:0000305|PubMed:19015515, ECO:0000305|PubMed:26228148}.
CC -!- DISEASE: Nemaline myopathy 3 (NEM3) [MIM:161800]: A form of nemaline
CC myopathy. Nemaline myopathies are muscular disorders characterized by
CC muscle weakness of varying severity and onset, and abnormal thread-like
CC or rod-shaped structures in muscle fibers on histologic examination.
CC {ECO:0000269|PubMed:10508519, ECO:0000269|PubMed:11166164,
CC ECO:0000269|PubMed:11333380, ECO:0000269|PubMed:15198992,
CC ECO:0000269|PubMed:15236405, ECO:0000269|PubMed:15336687,
CC ECO:0000269|PubMed:15520409, ECO:0000269|PubMed:16427282,
CC ECO:0000269|PubMed:16945537, ECO:0000269|PubMed:17705262,
CC ECO:0000269|PubMed:22442437, ECO:0000269|PubMed:23650303,
CC ECO:0000269|PubMed:25635128, ECO:0000269|PubMed:25938801,
CC ECO:0000269|PubMed:29274205}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, actin, congenital, with excess of thin myofilaments
CC (MPCETM) [MIM:161800]: A congenital muscular disorder characterized at
CC histological level by areas of sarcoplasm devoid of normal myofibrils
CC and mitochondria, and replaced with dense masses of thin filaments.
CC Central cores, rods, ragged red fibers, and necrosis are absent.
CC {ECO:0000269|PubMed:10508519}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, congenital, with fiber-type disproportion (CFTD)
CC [MIM:255310]: A genetically heterogeneous disorder in which there is
CC relative hypotrophy of type 1 muscle fibers compared to type 2 fibers
CC on skeletal muscle biopsy. However, these findings are not specific and
CC can be found in many different myopathic and neuropathic conditions.
CC {ECO:0000269|PubMed:15468086, ECO:0000269|PubMed:17387733}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myopathy, scapulohumeroperoneal (SHPM) [MIM:616852]: An
CC autosomal dominant muscular disorder characterized by progressive
CC muscle weakness with initial scapulo-humeral-peroneal and distal
CC distribution. Over time, muscle weakness progresses to proximal muscle
CC groups. Clinical characteristics include scapular winging, mild lower
CC facial weakness, foot drop due to foot eversion and dorsiflexion
CC weakness, and selective muscle atrophy. Age at onset and disease
CC progression are variable. {ECO:0000269|PubMed:25938801}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms, alpha,
CC beta and gamma have been identified. The alpha actins are found in
CC muscle tissues and are a major constituent of the contractile
CC apparatus. The beta and gamma actins coexist in most cell types as
CC components of the cytoskeleton and as mediators of internal cell
CC motility.
CC -!- SIMILARITY: Belongs to the actin family. {ECO:0000305}.
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DR EMBL; J00068; AAB59376.1; -; mRNA.
DR EMBL; M20543; AAA60296.1; -; Genomic_DNA.
DR EMBL; AF182035; AAF02694.1; -; Genomic_DNA.
DR EMBL; CR536516; CAG38754.1; -; mRNA.
DR EMBL; CR541796; CAG46595.1; -; mRNA.
DR EMBL; AL160004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69898.1; -; Genomic_DNA.
DR EMBL; BC012597; AAH12597.1; -; mRNA.
DR CCDS; CCDS1578.1; -.
DR PIR; A31251; ATHU.
DR RefSeq; NP_001091.1; NM_001100.3.
DR PDB; 7RNS; X-ray; 1.14 A; B=52-60.
DR PDB; 7RNU; X-ray; 1.45 A; B/D/F/H=52-60.
DR PDB; 7RNV; X-ray; 2.15 A; B=52-60.
DR PDBsum; 7RNS; -.
DR PDBsum; 7RNU; -.
DR PDBsum; 7RNV; -.
DR AlphaFoldDB; P68133; -.
DR SMR; P68133; -.
DR BioGRID; 106573; 236.
DR IntAct; P68133; 46.
DR MINT; P68133; -.
DR STRING; 9606.ENSP00000355645; -.
DR DrugBank; DB04151; 1-Methylhistidine.
DR DrugBank; DB04629; Aplyronine A.
DR DrugBank; DB03850; Jaspisamide A.
DR DrugBank; DB03616; Kabiramide C.
DR DrugBank; DB02621; Latrunculin A.
DR DrugBank; DB08080; Latrunculin B.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugBank; DB04774; Reidispongiolide A.
DR DrugBank; DB04775; Reidispongiolide C.
DR DrugBank; DB04783; Sphinxolide B.
DR DrugBank; DB02772; Sucrose.
DR DrugBank; DB03903; Tmr.
DR DrugBank; DB03021; Ulapualide A.
DR GlyGen; P68133; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; P68133; -.
DR PhosphoSitePlus; P68133; -.
DR SwissPalm; P68133; -.
DR BioMuta; ACTA1; -.
DR DMDM; 61218043; -.
DR EPD; P68133; -.
DR jPOST; P68133; -.
DR MassIVE; P68133; -.
DR MaxQB; P68133; -.
DR PaxDb; P68133; -.
DR PeptideAtlas; P68133; -.
DR PRIDE; P68133; -.
DR ProteomicsDB; 57532; -.
DR Antibodypedia; 3508; 1341 antibodies from 45 providers.
DR DNASU; 58; -.
DR Ensembl; ENST00000366684.7; ENSP00000355645.3; ENSG00000143632.15.
DR GeneID; 58; -.
DR KEGG; hsa:58; -.
DR MANE-Select; ENST00000366684.7; ENSP00000355645.3; NM_001100.4; NP_001091.1.
DR UCSC; uc001htm.4; human.
DR CTD; 58; -.
DR DisGeNET; 58; -.
DR GeneCards; ACTA1; -.
DR HGNC; HGNC:129; ACTA1.
DR HPA; ENSG00000143632; Tissue enriched (skeletal).
DR MalaCards; ACTA1; -.
DR MIM; 102610; gene.
DR MIM; 161800; phenotype.
DR MIM; 255310; phenotype.
DR MIM; 616852; phenotype.
DR neXtProt; NX_P68133; -.
DR OpenTargets; ENSG00000143632; -.
DR Orphanet; 171439; Childhood-onset nemaline myopathy.
DR Orphanet; 2020; Congenital fiber-type disproportion myopathy.
DR Orphanet; 98904; Congenital myopathy with excess of thin filaments.
DR Orphanet; 171433; Intermediate nemaline myopathy.
DR Orphanet; 447977; Progressive scapulohumeroperoneal distal myopathy.
DR Orphanet; 97244; Rigid spine syndrome.
DR Orphanet; 171430; Severe congenital nemaline myopathy.
DR Orphanet; 171436; Typical nemaline myopathy.
DR Orphanet; 97240; Zebra body myopathy.
DR PharmGKB; PA24455; -.
DR VEuPathDB; HostDB:ENSG00000143632; -.
DR eggNOG; KOG0676; Eukaryota.
DR GeneTree; ENSGT00940000156048; -.
DR InParanoid; P68133; -.
DR OMA; DESHACE; -.
DR OrthoDB; 649708at2759; -.
DR PhylomeDB; P68133; -.
DR TreeFam; TF354237; -.
DR PathwayCommons; P68133; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; P68133; -.
DR SIGNOR; P68133; -.
DR BioGRID-ORCS; 58; 16 hits in 1077 CRISPR screens.
DR ChiTaRS; ACTA1; human.
DR EvolutionaryTrace; P68133; -.
DR GeneWiki; Actin,_alpha_1; -.
DR GenomeRNAi; 58; -.
DR Pharos; P68133; Tbio.
DR PRO; PR:P68133; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P68133; protein.
DR Bgee; ENSG00000143632; Expressed in skeletal muscle tissue of biceps brachii and 132 other tissues.
DR ExpressionAtlas; P68133; baseline and differential.
DR Genevisible; P68133; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IMP:UniProtKB.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0044297; C:cell body; ISS:AgBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005869; C:dynactin complex; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:AgBase.
DR GO; GO:0030027; C:lamellipodium; ISS:AgBase.
DR GO; GO:0030017; C:sarcomere; IDA:UniProtKB.
DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB.
DR GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; TAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; TAS:UniProtKB.
DR GO; GO:0017022; F:myosin binding; TAS:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
DR GO; GO:0071417; P:cellular response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0090131; P:mesenchyme migration; ISS:AgBase.
DR GO; GO:0006936; P:muscle contraction; TAS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:AgBase.
DR GO; GO:0009991; P:response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0010226; P:response to lithium ion; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR GO; GO:0043503; P:skeletal muscle fiber adaptation; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0030240; P:skeletal muscle thin filament assembly; IMP:UniProtKB.
DR InterPro; IPR004000; Actin.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR004001; Actin_CS.
DR InterPro; IPR043129; ATPase_NBD.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00406; ACTINS_1; 1.
DR PROSITE; PS00432; ACTINS_2; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; Cytoskeleton;
KW Disease variant; Isopeptide bond; Methylation; Muscle protein;
KW Nemaline myopathy; Nucleotide-binding; Oxidation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..377
FT /note="Actin, alpha skeletal muscle, intermediate form"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT /id="PRO_0000442803"
FT CHAIN 3..377
FT /note="Actin, alpha skeletal muscle"
FT /evidence="ECO:0000250|UniProtKB:P68135"
FT /id="PRO_0000442804"
FT REGION 112..125
FT /note="Interaction with alpha-actinin"
FT /evidence="ECO:0000250|UniProtKB:P68135"
FT REGION 360..372
FT /note="Interaction with alpha-actinin"
FT /evidence="ECO:0000250|UniProtKB:P68135"
FT MOD_RES 2
FT /note="N-acetylcysteine; in intermediate form"
FT /evidence="ECO:0000250|UniProtKB:P62737"
FT MOD_RES 46
FT /note="Methionine (R)-sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P68134"
FT MOD_RES 49
FT /note="Methionine (R)-sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P68134"
FT MOD_RES 63
FT /note="N6-malonyllysine"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 75
FT /note="Tele-methylhistidine"
FT /evidence="ECO:0000269|PubMed:30626964"
FT MOD_RES 86
FT /note="N6-methyllysine"
FT /evidence="ECO:0000269|PubMed:23673617"
FT CROSSLNK 52
FT /note="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain
FT with E-272); by Vibrio toxins RtxA and VgrG1"
FT /evidence="ECO:0000250|UniProtKB:P60709"
FT CROSSLNK 272
FT /note="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain
FT with K-52); by Vibrio toxins RtxA and VgrG1"
FT /evidence="ECO:0000250|UniProtKB:P60709"
FT VARIANT 3
FT /note="D -> Y (in NEM3; some patients have core lesions on
FT muscle biopsy; dbSNP:rs121909527)"
FT /evidence="ECO:0000269|PubMed:15520409"
FT /id="VAR_062424"
FT VARIANT 17
FT /note="G -> R (in MPCETM; dbSNP:rs121909521)"
FT /evidence="ECO:0000269|PubMed:10508519"
FT /id="VAR_011680"
FT VARIANT 17
FT /note="G -> S (in NEM3)"
FT /evidence="ECO:0000269|PubMed:29274205"
FT /id="VAR_085717"
FT VARIANT 27
FT /note="D -> N (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062425"
FT VARIANT 37
FT /note="V -> L (in NEM3; dbSNP:rs1553255521)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062426"
FT VARIANT 40
FT /note="P -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062427"
FT VARIANT 42
FT /note="H -> Y (in NEM3; severe)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405"
FT /id="VAR_015579"
FT VARIANT 43
FT /note="Q -> R (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062428"
FT VARIANT 44
FT /note="G -> V (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062429"
FT VARIANT 45
FT /note="V -> F (in NEM3; dbSNP:rs398123562)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062430"
FT VARIANT 66
FT /note="I -> N (in NEM3; dbSNP:rs1553255502)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062431"
FT VARIANT 68
FT /note="T -> I (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15198992"
FT /id="VAR_062432"
FT VARIANT 72
FT /note="P -> R (in NEM3)"
FT /evidence="ECO:0000269|PubMed:25635128"
FT /id="VAR_083589"
FT VARIANT 74
FT /note="E -> K (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15198992"
FT /id="VAR_062433"
FT VARIANT 75
FT /note="H -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062434"
FT VARIANT 75
FT /note="H -> R (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062435"
FT VARIANT 77
FT /note="I -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15236405"
FT /id="VAR_062436"
FT VARIANT 79
FT /note="T -> A (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062437"
FT VARIANT 85
FT /note="E -> K (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15236405"
FT /id="VAR_062438"
FT VARIANT 96
FT /note="L -> P (in NEM3; autosomal recessive;
FT dbSNP:rs121909519)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_011681"
FT VARIANT 116
FT /note="A -> T (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062439"
FT VARIANT 116
FT /note="A -> V (in NEM3)"
FT /evidence="ECO:0000269|PubMed:25635128"
FT /id="VAR_083590"
FT VARIANT 117
FT /note="N -> S (in NEM3; autosomal dominant;
FT dbSNP:rs121909520)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:11333380, ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15198992"
FT /id="VAR_011682"
FT VARIANT 117
FT /note="N -> T (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062440"
FT VARIANT 118
FT /note="R -> H (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062441"
FT VARIANT 134
FT /note="M -> V (in NEM3; autosomal dominant)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:11166164, ECO:0000269|PubMed:12921789"
FT /id="VAR_013470"
FT VARIANT 136
FT /note="V -> A (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062442"
FT VARIANT 138
FT /note="I -> M (in NEM3; autosomal recessive;
FT dbSNP:rs121909526)"
FT /evidence="ECO:0000269|PubMed:11333380,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992"
FT /id="VAR_011683"
FT VARIANT 140
FT /note="A -> P (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062443"
FT VARIANT 142
FT /note="L -> P (in NEM3; dbSNP:rs1553255482)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062444"
FT VARIANT 148
FT /note="G -> D (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062445"
FT VARIANT 150
FT /note="T -> N (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062446"
FT VARIANT 156
FT /note="D -> N (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062447"
FT VARIANT 165
FT /note="V -> L (in MPCETM; dbSNP:rs121909522)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992"
FT /id="VAR_011684"
FT VARIANT 165
FT /note="V -> M (in NEM3; results in sequestration of
FT sarcomeric and Z line proteins into intranuclear
FT aggregates; there is some evidence of muscle regeneration
FT suggesting a compensatory effect; dbSNP:rs121909522)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15198992, ECO:0000269|PubMed:16427282,
FT ECO:0000269|PubMed:17705262"
FT /id="VAR_062448"
FT VARIANT 172
FT /note="A -> G (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062449"
FT VARIANT 181
FT /note="D -> G (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15236405"
FT /id="VAR_062450"
FT VARIANT 181
FT /note="D -> H (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062451"
FT VARIANT 181
FT /note="D -> N (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062452"
FT VARIANT 184
FT /note="G -> D (in NEM3; mild)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405"
FT /id="VAR_015580"
FT VARIANT 185
FT /note="R -> C (in NEM3; severe; dbSNP:rs1064794287)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_015582"
FT VARIANT 185
FT /note="R -> D (in NEM3; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_062453"
FT VARIANT 185
FT /note="R -> G (in NEM3; autosomal dominant; severe)"
FT /evidence="ECO:0000269|PubMed:11333380,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_015581"
FT VARIANT 185
FT /note="R -> S (in NEM3; dbSNP:rs1064794287)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062454"
FT VARIANT 197
FT /note="E -> D (in SHPM; no effect on cytoskeleton
FT structure; dbSNP:rs869312739)"
FT /evidence="ECO:0000269|PubMed:25938801"
FT /id="VAR_076426"
FT VARIANT 198
FT /note="R -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062455"
FT VARIANT 199
FT /note="G -> S (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15236405"
FT /id="VAR_062456"
FT VARIANT 223
FT /note="L -> P (in CFTD; dbSNP:rs121909530)"
FT /evidence="ECO:0000269|PubMed:15468086"
FT /id="VAR_032917"
FT VARIANT 226
FT /note="E -> G (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062457"
FT VARIANT 226
FT /note="E -> Q (in NEM3; dbSNP:rs1057521118)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062458"
FT VARIANT 227
FT /note="N -> V (in NEM3; requires 2 nucleotide
FT substitutions)"
FT /id="VAR_062459"
FT VARIANT 229
FT /note="M -> I (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062460"
FT VARIANT 229
FT /note="M -> T (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062461"
FT VARIANT 229
FT /note="M -> V (in NEM3; dbSNP:rs794727714)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062462"
FT VARIANT 243
FT /note="E -> K (in NEM3; dbSNP:rs367543051)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062463"
FT VARIANT 248
FT /note="Q -> K (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062464"
FT VARIANT 248
FT /note="Q -> R (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062465"
FT VARIANT 253
FT /note="G -> D (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062466"
FT VARIANT 258
FT /note="R -> H (in NEM3; severe)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_015583"
FT VARIANT 258
FT /note="R -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062467"
FT VARIANT 261
FT /note="E -> V (in NEM3; autosomal recessive;
FT dbSNP:rs121909523)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_011685"
FT VARIANT 265
FT /note="Q -> L (in NEM3; severe)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_015584"
FT VARIANT 270
FT /note="G -> C (in NEM3; autosomal dominant;
FT dbSNP:rs121909525)"
FT /evidence="ECO:0000269|PubMed:11333380,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_011686"
FT VARIANT 270
FT /note="G -> D (in NEM3)"
FT /evidence="ECO:0000269|PubMed:15336687"
FT /id="VAR_062468"
FT VARIANT 270
FT /note="G -> R (in NEM3; dbSNP:rs121909525)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062469"
FT VARIANT 271
FT /note="M -> R (in NEM3; autosomal dominant;
FT dbSNP:rs1553255360)"
FT /evidence="ECO:0000269|PubMed:11166164,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_013471"
FT VARIANT 274
FT /note="A -> E (in NEM3; dbSNP:rs1553255357)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062470"
FT VARIANT 281
FT /note="Y -> H (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062471"
FT VARIANT 282
FT /note="N -> K (in NEM3; severe)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405"
FT /id="VAR_015585"
FT VARIANT 285
FT /note="M -> K (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062472"
FT VARIANT 288
FT /note="D -> G (in NEM3; severe; formation of rod-like
FT structure)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15236405,
FT ECO:0000269|PubMed:25938801"
FT /id="VAR_015586"
FT VARIANT 294
FT /note="D -> V (in CFTD; results in decreased motility due
FT to abnormal interactions between actin and tropomyosin with
FT tropomyosin stabilized in the 'off' position; the mutant
FT protein incorporates into actin filaments and does not
FT result in increased actin aggregation or disruption of the
FT sarcomere; dbSNP:rs121909529)"
FT /evidence="ECO:0000269|PubMed:15468086,
FT ECO:0000269|PubMed:17387733"
FT /id="VAR_032918"
FT VARIANT 328
FT /note="K -> N (in NEM3; no effect on actin structure;
FT higher sensitivity to calcium; dbSNP:rs398122936)"
FT /evidence="ECO:0000269|PubMed:22442437"
FT /id="VAR_076427"
FT VARIANT 334
FT /note="P -> S (in CFTD; dbSNP:rs121909531)"
FT /evidence="ECO:0000269|PubMed:15468086"
FT /id="VAR_032919"
FT VARIANT 336
FT /note="E -> A (in NEM3; dbSNP:rs121909528)"
FT /evidence="ECO:0000269|PubMed:15520409"
FT /id="VAR_062473"
FT VARIANT 338
FT /note="K -> E (in NEM3)"
FT /evidence="ECO:0000269|PubMed:16945537"
FT /id="VAR_062474"
FT VARIANT 338
FT /note="K -> I (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062475"
FT VARIANT 350
FT /note="S -> L (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062476"
FT VARIANT 358
FT /note="W -> C (in NEM3; found in a patient with a rare
FT combination of NEM3 and dilated cardiomyopathy;
FT dbSNP:rs587777354)"
FT /evidence="ECO:0000269|PubMed:23650303"
FT /id="VAR_076428"
FT VARIANT 359
FT /note="I -> L (in NEM3; autosomal dominant; severe;
FT dbSNP:rs121909524)"
FT /evidence="ECO:0000269|PubMed:11333380,
FT ECO:0000269|PubMed:12921789, ECO:0000269|PubMed:15198992"
FT /id="VAR_015587"
FT VARIANT 372
FT /note="V -> F (in NEM3; severe)"
FT /evidence="ECO:0000269|PubMed:10508519,
FT ECO:0000269|PubMed:12921789"
FT /id="VAR_011687"
FT VARIANT 374
FT /note="R -> S (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789"
FT /id="VAR_062477"
FT VARIANT 375
FT /note="K -> E (in NEM3; dbSNP:rs1571892209)"
FT /evidence="ECO:0000269|PubMed:15336687"
FT /id="VAR_062478"
FT VARIANT 375
FT /note="K -> Q (in NEM3)"
FT /evidence="ECO:0000269|PubMed:12921789,
FT ECO:0000269|PubMed:15236405"
FT /id="VAR_062479"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:7RNS"
SQ SEQUENCE 377 AA; 42051 MW; DF2A3A046346A179 CRC64;
MCDEDETTAL VCDNGSGLVK AGFAGDDAPR AVFPSIVGRP RHQGVMVGMG QKDSYVGDEA
QSKRGILTLK YPIEHGIITN WDDMEKIWHH TFYNELRVAP EEHPTLLTEA PLNPKANREK
MTQIMFETFN VPAMYVAIQA VLSLYASGRT TGIVLDSGDG VTHNVPIYEG YALPHAIMRL
DLAGRDLTDY LMKILTERGY SFVTTAEREI VRDIKEKLCY VALDFENEMA TAASSSSLEK
SYELPDGQVI TIGNERFRCP ETLFQPSFIG MESAGIHETT YNSIMKCDID IRKDLYANNV
MSGGTTMYPG IADRMQKEIT ALAPSTMKIK IIAPPERKYS VWIGGSILAS LSTFQQMWIT
KQEYDEAGPS IVHRKCF
